In March, 2013, doctors reported that a Mississippi-born child treated early and aggressively for HIV had been effectively cured of the virus. Now, the child's doctors say the infection has returned.

"It felt very much like a punch to the gut," said Dr. Hannah Gay of the University of Mississippi, who initially handled the child's case at the University's Medical Center and has continued seeing her since she was apparently cured.

"It was disappointing from the scientific standpoint because we had been hopeful it would lead to bigger and better things, but mainly for the sake of the child who is back on medicine and expected to remain on medicine for a very long time."

As we noted when the news first broke in 2013, the Mississippi child's case was unique for several reasons that extended beyond her apparent cure. The child's treatment began quickly, within thirty hours of her birth. Recognizing that the child was at a high risk of infection, Gay ordered the child receive an aggressive cocktail of antiretroviral (ARV) medications before she received the blood results that would later confirm the child was, in fact, HIV+.

By 29 days of age, HIV levels in the girl's blood had fallen so low as to be undetectable by routine lab tests. The results were promising – but then the child and her mother began missing regularly scheduled appointments. By 18 months of age the child's mother had ceased bringing her in altogether. When Gay finally tracked the pair down, the child was nearly 2 and had gone without her ARV therapy for about five months. But when Gay ordered HIV tests they all came back negative. Unable to believe the result, she asked immunologists to check her work. Their tests found traces of the HIV, but researchers believed whatever virus remained to be incapable of multiplying or spreading to other people. Under these assumptions, the girl's doctors claimed the girl to be "effectively" cured.

But now, at age four, the girl is showing signs of infection for the first time since her birth in 2010.

The news is of course crushing, but researchers emphasize the child's unconventional treatment was not for nothing. By treating as early and aggressively as they did, the child's doctors may have slowed the progression of the virus and spared her years of treatment with drug cocktails notorious for their debilitating side effects.

"The fact that this child was able to remain off antiretroviral treatment for two years and maintain quiescent virus for that length of time is unprecedented," said Dr. Deborah Persaud of John Hopkins Children's Center in Baltimore, who first presented the child's case. "Typically, when treatment is stopped, HIV levels rebound within weeks, not years."

If reproducing the Mississippi girl's recovery in other infants seemed ethically fraught before, the return of the virus only makes it more so now. As we noted previously, the scientific process demands that "the first and most important course of action... should not be to implement this child's treatment on everyone worldwide, but rather to replicate her incredible recovery in other children." The return of the virus serves as a punishing reminder that doing so will almost definitely require more than mimicking the Mississippi girl's therapy.

"Scientifically, this development reminds us that we still have much more to learn about the intricacies of HIV infection and where the virus hides in the body," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID). "The NIH remains committed to moving forward with research on a cure for HIV infection."